The research objectives of this project are to study reaction to injury in the nephron. These studies include sublethal and lethal reactions to injury with emphasis on early changes and factors which promote the reversibility and modify this type of response. An important facet of the studies regards delineation of the pathogenesis of cellular events following injury, the interdependence between these events, the differences in the sequence of changes following different types of injury. The project also includes studies exploring various hypotheses of loss of reversibility of hypotheses to explain the "point- of-no-return" and pharmacologic factors that modify the cellular response. Central to the project is the study of structural and functional changes in cell membranes including studies of membrane organization and order of membrane components. In other studies we are correlating cellular compositional changes with levels and ratios of adenine nucleotides and all of this information will be correlated with conformational change in cell organelles.